Recent epidemiological studies show that short sleep duration (d5-7 h/night) correlates with overweight and obesity, such that individuals with short sleep periods tend to have a higher body mass index (BMI) than those who sleep 8-9 h/night. The mechanism for this relationship is currently unknown. However, energy balance must be disrupted to produce weight gain. Therefore, the purpose of this study is to examine the impact of short sleep duration, 4 h/night, relative to habitual sleep duration of 8-9 h/night, on energy balance. The major aims of this study are to compare energy expenditure and energy intake during the periods of habitual and short sleep duration and to examine the neural and hormonal pathways involved in eating behavior under periods of habitual and short sleep. Men and women, 30-45 y and BMI {22-25} kg/m2, will be recruited to participate in this randomized, crossover study of short and habitual sleep periods. During each period of {5} nights, subjects will be required to sleep at the laboratory under supervision. During this time, subjects will be total inpatients to ensure compliance with the protocol. Each sleep duration period will be separated by a 2-4-wk washout period. On the first day of each phase, subjects will be given a dose of doubly-labeled water to measure free-living energy expenditure over the 6-d period. {During the first 4 days, energy intake will be controlled and meals served at fixed times. The last 2 days will be ad libitum feeding of self-selected meals.} Hormones, including leptin, insulin, ghrelin, {PYY, adiponectin, and GLP-1} will be assessed daily in the fasted state {and, on day 4, over a 24- hour period, while subjects are consuming a controlled diet with fixed meal times}. Functional magnetic resonance imaging measurements of brain activity in response to food stimuli will be done on day 5 to examine brain regions associated with motivation to eat. On day 5, subjects will undergo measurements of {basal metabolic rate using indirect calorimetry}. Ad libitum energy intakes will be assessed on days 5 and 6. Polysomnographic monitoring will be performed nightly {to assess sleep duration}. Mediation analyses will allow us to determine whether hormone levels are related to and predictive of energy expenditure and energy intake data. The measurements performed in this study will allow us to determine how reduced sleep periods can impact energy balance and potentially lead to changes in body weight. As such, it will provide comprehensive information of the neural, physiological, hormonal, and behavioral networks related to energy balance and which are affected by sleep duration. PUBLIC HEALTH RELEVANCE: Observational and epidemiological studies have found a link between obesity and short sleep duration with the prevalence of both increasing in the past decades. At this time, it is unknown whether short sleep is a cause of obesity and how short sleep would lead to obesity. Some studies associate short sleep with increased levels of hormone that stimulate appetite. This study will examine how food intake and energy expenditure can be modified by sleep duration as a means of understanding a potential causal pathway.